There is mounting evidence implicating a role for the immune system in autism. This evidence includes a genetic predisposition, association of HLA genes on chromosome 6, anecdotal accounts of microbial infections, a distribution based on sex (autism is four to five times more frequent in boys than girls), and more recently, an immune-based enteropathy. [unreadable] [unreadable] Our laboratory has made several findings that support an immune deficiency-autoimmune basis for at least some cases of autism. A recent experiment suggests that the class II HLA-DR4 allele is associated and, more importantly, linked to autism spectrum disorder by the transmission disequilibrium test (TDT) (Torres, 2002). As the DR4 is part of the shared epitope (SE) the investigators have analyzed high-resolution typing data for SE specificities. Examination of Autism Genetic Resource Exchange (AGRE) families suggest that the SE is linked to autism (P=0.00330) through the maternal chromosomes by the TDT. Analysis of the class I region in 111 families showed highly significant autism association with HLA-A2 (P=0.0003). Although these results are encouraging, all of the investigators' data comes from Caucasian volunteers. HLA allelic frequencies vary significantly in different racial/ethnic groups. Analysis of HLA allelic frequencies in White Hispanics and African Americans could add significantly to our understanding of HLA genes in autism. [unreadable] [unreadable] Our long-term objectives involve examination of other genes in the HLA region and the determination of autism HLA associations in other racial groups. The co-investigator has an ongoing project (CDC funded) where birth blood spots are retrieved for cytokine and neutropin analysis after children receive an autism diagnoses. The proposed project will be an extension of the principal investigator's immunogenetic research and contribute to the co-investigator's overall project. Together, the investigators have adapted a new DNA amplification system (Multiple Displacement Amplification) in collaboration with Dr. David Ward (Yale University) that allows for typing from minute amounts of blood spot extracted DNA. This project will be the first to examine HLA alleles in ethnic minorities afflicted with autism. These studies are health related in the sense that addition information about immune abnormalities may lead to new approaches for immune treatment of autism. [unreadable] [unreadable]